11-methoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline | 53581-12-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 英文名称: 11-methoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
• 英文别名: 11-Methoxynoraporphin；11-methoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
• CAS: 53581-12-7
• 化学式: C₁₇H₁₇NO
• 分子量: 251.328
• InChiKey: WJLQHAGLYICAJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  11-methoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 (S)-11-methoxy-N-allylnoraporphine
  参考文献：
  名称：

  (R)- and (S)-enantiomers of 11-hydroxy- and 10,11-dihydroxy-N-allylnoraporphine: synthesis and affinity for dopamine receptors in rat brain tissue

  摘要：

  The R-(-)- and S-(+)-enantiomers of 11-hydroxy-N-allyl (4), and 10,11-dihydroxy-N-allyl (3) congeners of 11-hydroxy-N-n-propylnoraporphine (11-OH-NPa, 2) or N-n-propylnorapomorphine (NPA, 1) were synthesized. Binding affinity of these compounds at dopamine (DA) receptor sites was evaluated with a membrane preparation of corpus striatum from rat brain. The R/S enantiomeric receptor affinity ratio was enhanced by allylic substitution of 3 and 4 and their R isomers had high DA receptor affinity similar to that of the N-n-propyl congeners. These N-allylaporphines are proposed as useful precursors to the preparation of their tritiated N-n-propyl enantiomers.

  DOI：

  10.1021/jm00105a005
• 作为产物：
  描述：

  在 palladium on activated charcoal 氢气 作用下， 以 溶剂黄146 为溶剂， 生成 11-methoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
  参考文献：
  名称：

  11-Substituted (R)-Aporphines:  Synthesis, Pharmacology, and Modeling of D_2A and 5-HT_1A Receptor Interactions

  摘要：

  A series of C11-substituted (R)-aporphines and C11-oxygenated (R)-noraporphines has been synthesized and evaluated for central serotonergic and dopaminergic effects in vitro and in vivo. The various C11-substituents were introduced using efficient nickel- and palladium-catalyzed reactions of the corresponding triflate (R)-11-[[(trifluoromethyl)sulfonyl]oxy] aporphine (6), Several compounds display high affinity to serotonin 5-HT1A receptors in spite of major differences in steric bulk and electronic properties of the various C11-substituents. A change of the N-methyl group of the nonselective 3 to H [23, (R)-11-hydroxynoraporphine] or propyl [2, (R)-11-hydroxy-N-propylnoraporphine] increases the selectivity for 5-HT1A receptors (100-fold) and dopamine D-2A receptors (3-fold), respectively. Compounds 3 and 23 have similar affinities to 5-HT1A receptors, whereas the propyl substituent of 2 not only enhances the selectivity for D-2A receptors but also increases the D-2A affinity. Modeling of ligand-receptor binding site interactions yielded an interaction site model for the 5-HT1A receptor that describes a gradual change in binding mode for C11-hydroxy, -methoxy-, and -phenyl-substituted derivatives. Hydrogen bonding is hereby gradually replaced by van der Waals interactions involving a relatively large lipophilic pocket. The derived D-2A receptor model can accommodate both the N-propyl substituent of 2 and the C11-ethyl substituent of 11 [(R)-11-ethylaporphine].

  DOI：

  10.1021/jm960189i

文献信息

• NEUMEYER, JOHN L.;GAO, YIGONG;KULA, NORA S.;BALDESSARINI, ROSS J., J. MED. CHEM., 34,(1991) N, C. 24-28
  作者：NEUMEYER, JOHN L.、GAO, YIGONG、KULA, NORA S.、BALDESSARINI, ROSS J.

  DOI：——

  日期：——
• 11-Substituted (<i>R</i>)-Aporphines:  Synthesis, Pharmacology, and Modeling of D_2A and 5-HT_1A Receptor Interactions
  作者：Martin H. Hedberg、Tero Linnanen、Johanna M. Jansen、Gunnar Nordvall、Stephan Hjorth、Lena Unelius、Anette M. Johansson

  DOI：10.1021/jm960189i

  日期：1996.1.1

  A series of C11-substituted (R)-aporphines and C11-oxygenated (R)-noraporphines has been synthesized and evaluated for central serotonergic and dopaminergic effects in vitro and in vivo. The various C11-substituents were introduced using efficient nickel- and palladium-catalyzed reactions of the corresponding triflate (R)-11-[[(trifluoromethyl)sulfonyl]oxy] aporphine (6), Several compounds display high affinity to serotonin 5-HT1A receptors in spite of major differences in steric bulk and electronic properties of the various C11-substituents. A change of the N-methyl group of the nonselective 3 to H [23, (R)-11-hydroxynoraporphine] or propyl [2, (R)-11-hydroxy-N-propylnoraporphine] increases the selectivity for 5-HT1A receptors (100-fold) and dopamine D-2A receptors (3-fold), respectively. Compounds 3 and 23 have similar affinities to 5-HT1A receptors, whereas the propyl substituent of 2 not only enhances the selectivity for D-2A receptors but also increases the D-2A affinity. Modeling of ligand-receptor binding site interactions yielded an interaction site model for the 5-HT1A receptor that describes a gradual change in binding mode for C11-hydroxy, -methoxy-, and -phenyl-substituted derivatives. Hydrogen bonding is hereby gradually replaced by van der Waals interactions involving a relatively large lipophilic pocket. The derived D-2A receptor model can accommodate both the N-propyl substituent of 2 and the C11-ethyl substituent of 11 [(R)-11-ethylaporphine].
• (R)- and (S)-enantiomers of 11-hydroxy- and 10,11-dihydroxy-N-allylnoraporphine: synthesis and affinity for dopamine receptors in rat brain tissue
  作者：John L. Neumeyer、Nora S. Kula、Ross J. Baldessarini、Yigong Gao

  DOI：10.1021/jm00105a005

  日期：1991.1

  The R-(-)- and S-(+)-enantiomers of 11-hydroxy-N-allyl (4), and 10,11-dihydroxy-N-allyl (3) congeners of 11-hydroxy-N-n-propylnoraporphine (11-OH-NPa, 2) or N-n-propylnorapomorphine (NPA, 1) were synthesized. Binding affinity of these compounds at dopamine (DA) receptor sites was evaluated with a membrane preparation of corpus striatum from rat brain. The R/S enantiomeric receptor affinity ratio was enhanced by allylic substitution of 3 and 4 and their R isomers had high DA receptor affinity similar to that of the N-n-propyl congeners. These N-allylaporphines are proposed as useful precursors to the preparation of their tritiated N-n-propyl enantiomers.